See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/303522289

Veterinary Parasitic Vaccines -A Current Scenario

Article · January 2013

CITATIONS READS
0 375

1 author:

Dr Noor Alam Tufani

Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir
79 PUBLICATIONS   38 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Small ruminant Babesiosis View project

Diagnostic imaging View project

All content following this page was uploaded by Dr Noor Alam Tufani on 26 May 2016.

The user has requested enhancement of the downloaded file.

 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

Veterinary Parasitic Vaccines - A Current Scenario

Tarun Kumar, N. A. Tufani, Amit Prasad, Niddhi Arora, and V.S. Rajora
Department of Veterinary Medicine, College of Veterinary and Animal Sciences
G.B. Pant University of Agricultural and Technology, Pantnagar-263 145, U. S. Nagar, Uttarakhand

Abstract
Vaccinology combines disciplines of immunology, microbiology, protein chemistry, and molecular
biology with practical considerations of production costs, regulatory affairs, and commercial returns.
Veterinary vaccines already made enormous impacts not only on animal health, welfare, and production
but also on human health. To control parasitic diseases in animals, vaccines are considered as a better
alternative. However, most important barrier in the development of parasitic vaccine is incomplete
understanding of the molecular and immune regulatory pathways involved in the development of
immunity against parasitic diseases as well as lack of precise understanding of the host/parasite
interaction.
Keywords: Parasitic vaccines, Veterinary
Introduction
The term “vaccine” derived from the Latin word “vacca,” meaning cow) was first coined by Edward
Jenner. Vaccination helps in the development of acquired immunity by inoculating non-pathogenic but
immunogenic components of the pathogen, or closely related organisms.
The criteria for successful Veterinary vaccine preparation vary on the animal groups under consideration.
Criteria for companion animal vaccines are similar to those for human vaccines as in that the health and
welfare of the individual animal are of primary concern. On the other hand in case of livestock vaccines,
the main criteria are to improve overall production for the primary producers, and the cost-benefit results
from vaccination. Veterinary vaccines comprise only approximately 23% of the global market for animal
health products; the sector has grown consistently due to new technological advances in vaccine
development, the continuous development of drug resistance by pathogens, and the emergence of new
diseases (Meeusen et al., 2007). Parasitic diseases in livestock and companion animals are mainly
controlled and treated by chemotherapeutic agents. With the emergence of drug resistance among
different parasitic species, the situation is alarming (Sutherland and Leathwick, 2011). So safer and better
parasite control methods should be searched (Hoste and Torres-Acosta, 2011). Although, a large number
of vaccines against various pathogens including bacteria and virus are available in the market; but number
of anti-parasitic vaccines have remained low (Gerhardt, 2006). Therefore, vaccine against parasites has to
be developed and should be available in the market. This review mainly concentrates on general concepts
and recent advances in Veterinary parasitic vaccines.
Protozoal Vaccines
Protozoal infections in animals cause significant production losses. They create a major obstacle in the
5 Page

introduction of high-productivity breeds in poorer, mainly in tropical areas around the world. Many
 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

organisms also cause zoonotic diseases or have close relationships to human parasites, thereby increasing
their significance as infection reservoirs or animal models for human diseases. While no vaccines for
human protozoa are available yet, but number of veterinary vaccines are available in the market or have
been produced by Agriculture/Veterinary departments for local use (Meeusen et al., 2007). Most of these
vaccines are based on live organisms that stimulate an immune reaction in the hosts, mimicking natural
infections. However, an increasing number of killed subunit vaccines have been developed and
commercialized in recent years. The spectacular achievements in vaccines against cestodes and ticks
attracting attentions in the scientific community.
A. Live protozoal parasite vaccines
Immunological mechanisms involved in protection and the stages involved in protozoal infections have
mostly not been defined, so it is not surprising that most vaccines make use of the live organism itself to
elicit the required protective immune response. Vaccine development for these organisms becomes tough
as they display antigenic diversity in their different life cycle stages within the host as well as between
different species and strains and, within the same life cycle stage, in case of hemoprotozoal parasites.
Moreover protozoal parasites have a high degree of genetic complexity.
So these vaccines can be:
(i) Vaccines based on complete life cycle infections
Coccidiosis, being a major economic parasitic disease of poultry worldwide, is mainly controlled by
vaccination with low doses of infective organisms. Coccidiosis in poultry is caused by the obligate
intracellular protozoal parasite Eimeria species, which undergoes a defined number of asexual cycles of
merozoite production in gut epithelial cells (three to four merogenic cycles) before the final sexual stages
develop and produce the infective oocysts. As the infection is self-limiting, vaccination with small doses
of oocysts induces solid protection against homologous challenge with minimal pathology. Recently
developed live vaccines contain oocysts selected from naturally occurring Eimeria strains that produce
less merogenic cycles and are therefore safer to use. But the need for simultaneous administration is
needed to prevent infection of susceptible birds by vaccine-produced oocysts and species- and strain-
specific immunity as suggested by Shirley et al., 2005. The commercial success of this type of vaccine
lies primarily in breeder and layer flocks where anticoccidial drugs have been banned to prevent the
carryover of drugs into eggs and meat (Meeusen et al., 2007).
(ii) Vaccines based on drug-abbreviated infections
East Coast fever infection used to be controlled by vaccination of cattle with pathogenic wild-type
Theileria parva followed by drug treatment (long-acting tetracyclines). A solid protection (cell-mediated
6

immunity) was conferred against homologous challenge, but this vaccination strategy proved to be
Page

expensive as stated by Graham et al., 2006.

 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

(iii) Vaccines based on a truncated life cycle of parasites

Toxoplasma gondii infects a wide variety of hosts, including humans, and is the major cause of abortion
in sheep and goats. T. gondii parasites when continuously passages in mice found to have lost its ability to
form cysts. So incomplete S48 strain of T. gondii forms the basis of a commercial vaccine conferring
long-lasting immunity (18 months) of susceptible ewes against Toxoplasma-induced abortion when
administered prior to mating (Buxton and Innes, 1995).
(iv) Vaccines based on virulence-attenuated strains
Attenuated but still immunogenic piroplasms of Babesia bovis and Babesia bigemina were obtained after
continuous passaging in splenectomized calves. So Live vaccines using infected blood collected from
acute infections of splenectomized calves were developed in Australia several decades ago and are still
used in most countries to protect against babesiosis, as reviewed by Dalgliesh et al., 1981; de Waal and
Combrink, 2006.
This vaccine sometimes supplemented with A. Central infected blood where A. marginale is enzootic.
Many Veterinary institutes now produce frozen-blood vaccines stored in liquid nitrogen using either
dimethyl sulfoxide or glycerol as the cryoprotectant so that shelf life and safety can be ensured. It is
believed that a continuous exposure to natural tick infections is generally required to ensure continuous
and long-lasting immunity. Tropical theileriosis in cattle used to be controlled by a live, attenuated
Theileria annulata vaccine that has been produced by continuous in vitro passaging of the intracellular
macroschizont stage. (Pipano and Shkap, 2000).
B. Killed or subunit protozoal parasite vaccines.
Several inactivated vaccines consisting of crude whole organisms or, more recently, defined antigenic
structures are available in the animal market. But these vaccines are not as effective as live organisms but
they may form the basis for the development of recombinant vaccines. Neospora caninum is a major
cause of abortion in cattle (intermediate host). A crude N. caninum vaccine consisting of inactivated N.
caninum tachyzoites with an adjuvant available in the United States to aid in the reduction of N.
caninum-induced abortion in healthy pregnant cattle and prevent the transmission of the parasite to calves
in utero (Romero et al., 2004; Innes et al., 2005). Marsh et al., (2004) evaluated and proposed a vaccine
that alleviates equine protozoal myeloencephalitis caused by Sarcocystis neurona. Vaccine consists of in
vitro cultured merozoites, which are chemically inactivated, originally obtained from the spinal cord of a
horse, and mixed with a proprietary adjuvant.
Chronic infections that are resistant to chemotherapy can be treated through vaccination, (Olson et al.,
2000) and it is believed that vaccine acts mainly by neutralization of parasite toxins with antibodies.
7

Giardia intestinalis is an enteric parasite of many animal species and can cause severe gastrointestinal
Page

disease in young and immunocompromised individuals. GiardiaVax® a commercial vaccine has been
 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

licensed for use in dogs and cats that significantly reduce incidence, severity, and duration of cyst
shedding. The vaccine consists of a crude preparation of disrupted, axenically cultured G. intestinalis
trophozoites (sheep isolate).
Two subunit vaccines against canine babesiosis have been developed. Both vaccines consist of soluble
parasite antigens (SPA) that are released into the culture supernatant by in vitro-cultured parasites,
combined with adjuvant. The first vaccine released, Pirodog®, contains SPA from B. canis cultures only
(Moreau et al., 1989) whereas recently released NobivacPiro® contains SPA from B. Canis and Babesia
rossi in an attempt to broaden the strain-specific immunity. The protective effect of this vaccine seems to
be based on the antibody-dependent neutralization of a soluble parasite substance (Schetters, 2005).
Another subunit vaccine based on a strongly antigenic surface glycoprotein complex, fucose mannose
ligand (FML) antigen, from Leishmania donovani with saponin as adjuvant has been developed against
canine visceral leishmaniasis, in Brazil. Vaccine found to have 76 to 80% efficacy against both
homologous and heterologous challenge with L. chagasi and to last for at least 3.5 years (da Silva et al.,
2000). The vaccine may also havea therapeutic effectt on infected dogs.
A killed subunit vaccine has been developed against coccidiosis in poultry by ABIC Veterinary Products,
Israel (Wallach et al., 1995). The vaccine targets the final sexual, macrogametocyte stages that develop to
form the disease transmitting oocysts. This vaccine strategy works under the principle that it will allow
immunity against the asexual stages to be generated by natural infections while reducing oocyst shedding
and parasite transmission. Moreover protective immunoglobulins may be transferred into the egg yolk and
subsequently the hatchlings by immunizing laying hens, rather than the chicks so this considerably
reduces the number of vaccinations and animal handling. It is expensive to produce this type of vaccine as
it consists of affinity-purified native gametocyte antigens derived from infected chickens, and is still a
fairly complex preparation (Belli et al., 2002). To identify the protective components so to develop a
recombinant vaccine, three major components of affinity-purified native gametocyte antigens have
recently been cloned and characterized (Belli et al., 2004).
Helminth and Ectoparasite Vaccines
Foster and Elsheikha (2012) reviewed advances in the immune response to selected helminths of animal
health significance, and subsequent vaccine potential. Some important topics like helminths interaction
with the host immune system were assessed to better understand the pathogenesis of diseases caused by
helminths.
Mainly there are three different families of helminths i.e nematodes (roundworms), trematodes
(flatworms), and cestodes (tapeworms), that infect both animals and humans. Only one worm vaccine i.e.
8

against cattle lung nematode Dictyocaulus viviparous is available in the market and used in Europe. The
Page

vaccine contains irradiated L3-larvae that do not mature to adult worms (Ploeger, 2002). A similar
 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

approach was used to develop a vaccine against the canine intestinal nematode Ancylostoma caninum
(Miller, 1978) but it was observed that irradiation-attenuated larval vaccines developed against
gastrointestinal nematodes did not protect young, susceptible stock against infection and were, therefore,
never commercialized (Knox, 2000). Moreover larvae must be harvested from the manure of infected
animals so these vaccines are difficult to produce too. The increasing drug resistance of gastrointestinal
nematodes has renewed intense interest in developing vaccines for these important veterinary pathogens.
Commercial or field application of anticestode vaccines is still in progress. Effective recombinant
vaccines were developed against the cestodes Taenia ovis, T. saginata, T. solium and Echinococcus
granulosus. These vaccines are based on antigens of the parasite stage that adheres to the gut wall. When
used for vaccination, these antigens induce immune responses that interfere with successful attachment.
The vaccine against the cestode T. ovis has been registered in Australia and New Zealand, but has not
been marketed (Lightowlers et al., 2003).
Vaccine development against trematode species like liver flukes is hindered as they do not seem to induce
immunity in their natural ruminant hosts, even after repeated infections. New approaches need to be
developed to produce vaccines against these parasites.
Ectoparasitic arthropods would seem to be the ultimate challenge in vaccine development, as they not
only are large and complex but also spend most of their life outside or on the surface of the host. Vaccine
against the cattle tick, Boophilus microplus, is a recombinant vaccine based on a protein (Bm86) found in
the tick at the surface of the gut wall. It was first introduced commercially in Australia in 1994
(TickGUARD®; Fort Dodge Australia). This vaccine is unique in that it is not based on natural antigens
recognized by the immune system during infection but takes advantage of the ferocious blood-feeding
habits of the tick. Vaccination stimulates the production of high antibody levels in cattle against a tick gut
membrane-bound protein, Bm86, using a recombinant protein in a potent adjuvant.
These antibodies bind to the tick’s gut surface when taking a blood meal, causing the rupture of the gut
wall and tick death (Knox and Smith, 2001). The vaccine induces significant levels of protection against
tick infestation and, in some cases, against tick-borne diseases. However antibody levels are not boosted
by infection and need to be maintained at high levels by repeated immunization. Use of vaccine in
conjunction with drug administration, limits its practical and commercial use. Moreover the presence of a
tick immunoglobulin excretion system hampers the effectiveness of this vaccine approach in other ticks
(Nuttall et al., 2006).
Certain more barriers in parasitic vaccine development include that they have highly complex life cycles
and there is a general lack of precise understanding of the host/parasite interaction.
9

Efforts towards vaccine development should be pursued intensively. Many vaccines may find their
Page

greatest and most immediate application in integrated control strategies. The synergies offered by a
 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

combination of vaccines and parasiticides should be thoroughly explored, as this approach may lead to a
substantial reduction in the use of parasiticides.
References
Belli, S. I., Lee M., Thebo P., Wallach M. G., Schwartsburd B., and Smith N. C. 2002. Biochemical
characterisation of the 56 and 82 kDa immunodominant gametocyte antigens from Eimeria maxima. Int.
J. Parasitol. 32:805–816.
Belli, S. I., Mai K., Skene C. D., Gleeson M. T., Witcombe D. M., Katrib M., Finger A., Wallach M. G.,
and Smith N. C.. 2004. Characterisation of the antigenic and immunogenic properties of bacterially
expressed, sexual stage antigens of the coccidian parasite, Eimeria maxima. Vaccine. 22:4316–4325.
Buxton D., and Innes E. A. 1995. A commercial vaccine for ovine toxoplasmosis. Parasitology. 110:S11–
S16.
Da Silva, V. O., Borja-Cabrera G. P., Correia Pontes N. N., de Souza E. P., Luz K. G., Palatnik M., and
Palatnik de Sousa C. B.. 2000. A phase III trial of efficacy of the FML-vaccine against canine kala-azar in
an endemic area of Brazil (Sao Goncalo do Amaranto, RN). Vaccine. 19:1082–1092.
Dalgliesh, R. J., Callow L. L., Mellors L. T., and McGregor W. 1981. Development of a highly infective
Babesia bigemina vaccine of reduced virulence. Aust. Vet. J. 57:8–11.
De Waal, D. T., and Combrink M. P.. 2006. Live vaccines against bovine babesiosis. Vet. Parasitol.
138:88–96.
Gerhardt, R. 2006. West Nile virus in the United States (1999–2005). J Am. Anim. Hosp. Assoc. 42:170–
177.
Graham, S. P., Pelle R., Honda Y., Mwangi D. M., Tonukari N. J., Yamage M., Glew E. J., de Villiers E.
P., Shah T., Bishop R., Abuya E., Awino E., Gachanja J., Luyai A. E., Mbwika F., Muthiani A. M., D.
Ndegwa M., Njahira M., Nyanjui J. K., Onono F. O., Osaso J., Saya R. M., Wildmann C., Fraser C. M.,
Maudlin I., Gardner M. J., Morzaria S. P., Loosmore S., Gilbert S. C., Audonnet J. C., van der Bruggen
P., Nene V., and Taracha E. L.. 2006. Theileria parva candidate vaccine antigens recognized by immune
bovine cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA. 103:3286–3291.
Hoste, H., and Torres-Acosta, J.F. 2011. Non chemical control of helminths in ruminants: adapting
solutions for changing worms in a changing world. Vet Parasitol. 180:144–154
Innes, E. A., Wright S., Bartley P., Maley S., Macaldowie C., Esteban- Redondo I., and Buxton D. 2005.
The host-parasite relationship in bovine neosporosis. Vet. Immunol. Immunopathol. 108:29–36.
Knox D.P. & Smith W.D. (2001). – Vaccination against gastrointestinal nematode parasites of ruminants
using gut expressed antigens. Vet. Parasitol. 100 (1-2), 21-32.
Knox D.P. (2000). – Development of vaccines against gastrointestinal nematodes. Parasitology, 120
(Suppl.), S43-S61.
Lightowlers M.W., Colebrook A.L., Gauci C.G., Gauci S.M., Kyngdon C.T., Monkhouse J.L., Vallejo
Rodriquez C., Read A.J., Rolfe R.A. & Sato C. (2003). – Vaccination against cestode parasites: anti-
helminth vaccines that work and why. Vet. Parasitol. 115 (2), 83-123.
Marsh, A. E., Lakritz J., P. Johnson J., Miller M. A., Chiang Y. W., and Chu H. J. 2004. Evaluation of
immune responses in horses immunized using a killed Sarcocystis neurona vaccine. Vet. Ther. 5:34–42.
Meeusen Els. N. T., Walker J., Peters A., Pastoret P., and Jungersen G. 2007. Current Status of Veterinary
Vaccines. Clinical microbiology reviews. 20 (3) 489–510.
Miller T.A. (1978). Industrial development and field use of the canine hookworm vaccine. Adv.
Parasitol. 16: 333-342.
Moreau, Y., Vidor E., Bissuel G., and Dubreuil N. 1989. Vaccination against canine babesiosis: an
overview of field observations. Trans. R. Soc. Trop. Med. Hyg. 83(Suppl.):95–96.
10

Nuttall, P. A., Trimnell A. R., Kazimirova M., and Labuda M. 2006. Exposed and concealed antigens as
vaccine targets for controlling ticks and tick-borne diseases. Parasite Immunol. 28:155–163.
Page

Olson, M. E., Ceri H., and Morck D. W. 2000. Giardia vaccination. Parasitol. Today. 16:213–217.
 Vol 3(1) Jan’13
International Journal of Livestock Research ISSN 2277-1964 ONLINE www.ijlr.org

Pipano E., and Shkap V. 2000. Vaccination against tropical theileriosis. Ann. N. Y. Acad. Sci. 916:484–
500.
Ploeger H.W. (2002). – Dictyocaulus viviparus: re-emerging or never been away? Trends Parasitol. 18
(8), 329-332.
Romero, J. J., Perez E., and Frankena K. 2004. Effect of a killed whole Neospora caninum tachyzoite
vaccine on the crude abortion rate of Costa Rican dairy cows under field conditions. Vet. Parasitol.
123:149–159.
Schetters, T. 2005. Vaccination against canine babesiosis. Trends Parasitol. 21:179–184.
Shirley M. W., Smith A. L., and Tomley F. M. 2005. The biology of avian Eimeria with an emphasis on
their control by vaccination. Adv. Parasitol. 60:285–330.
Sutherland, I.A., and Leathwick, D.M. 2011. Anthelmintic resistance in nematode parasites of cattle: a
global issue? Trends Parasitol. 27:176–181.
Wallach, M., Smith N. C., Petracca M., Miller C. M., Eckert J., and Braun R. 1995. Eimeria maxima
gametocyte antigens: potential use in a subunit maternal vaccine against coccidiosis in chickens. Vaccine.
13:347–354.

11 Page

View publication stats